| 摘要: |
| 目的：利用UPLC-Q-TOF-MS及网络药理学与分子对接研究四海舒郁丸治疗甲状腺功能亢进症（以下简称甲亢）的物质基础和作用机制。方法：通过UPLC-Q-TOF-MS鉴定四海舒郁丸的活性成分，以口服生物利用度（OB）、类药性（DL）作为参数通过TSMSP数据库进行筛选，利用PubChem数据库下载符合标准的活性成分的sdf文件，通过SwissTargetPrediction数据库预测各活性成分作用靶点。通过OMIM、DisGenet、DrugBank、GeneCards数据库检索甲亢的疾病相关靶点。取药物靶点和疾病靶点的交集作为潜在靶点，并在STRING数据库中获得靶点-蛋白质相互作用网络图，导入Cytoscape软件获得关键靶点和有效成分，并进行基因本体（GO）功能和京都基因与基因组百科全书（KEGG）通路分析，最后利用分子对接进行验证。结果：共得到50种中药活性成分，其与甲亢有162个交集靶点。利用Cytoscape软件插件获得蛋白酪氨酸磷酸酶非受体11型（PTPN11）、胰岛素样生长因子1受体（IGF1R）、磷脂酰肌醇4，5-二磷酸3-激酶催化亚基α（PIK3CA）、表皮生长因子受体（EGFR）、蛋白激酶B1（AKT1）等12个四海舒郁丸中治疗甲亢的核心靶点。富集分析结果表明，四海舒郁丸通过磷脂酰肌醇3-激酶/蛋白激酶B信号通路、缺氧诱导因子1信号通路起到治疗甲亢的作用，而分子对接结果显示去氧地胆草素、黄柏酮、氧化小檗碱等与核心治疗靶点的分子结合力较强，为四海舒郁丸治疗甲亢的重要物质基础。结论：四海舒郁丸治疗甲亢的作用机制可能是其有效成分通过调节多个甲亢相关靶点，进而介导多条信号通路，从而治疗疾病。 |
| 关键词: 甲状腺功能亢进症 富碘中药 网络药理学 分子对接 |
| DOI： |
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| Mechanism of action of Sihai Shuyu pills in treatment of hyperthyroidism：A study based on UPLC-Q-TOF-MS，network pharmacology，and molecular docking |
| LIU Xiaoju,HUANG Wenbin,LI Xingjia |
| (Affiliated Hospital of Integrated Traditional Chinese and Western Medicine，Nanjing University of Chinese Medicine，Nanjing 210028，Jiangsu，China;State Key Laboratory of Syndrome Differentiation and Treatment of Gall Disease，Jiangsu Province Academy of Traditional Chinese Medicine，Nanjing 210028，Jiangsu，China) |
| Abstract: |
| Objective：To investigate the material basis and mechanism of action of Sihai Shuyu pills in the treatment of hyperthyroidism based on UPLC-Q-TOF-MS，network pharmacology，and molecular docking.Methods：UPLC-Q-TOF-MS was used to identify the active components of Sihai Shuyu pills，and oral bioavailability (OB) and drug-likeness (DL) were used as parameters for screening via TSMSP database.PubChem database was used to download the sdf documents of the active components meeting related criteria，and SwissTargetPrediction database was used to predict the action target of each active component.OMIM，DisGenet，DrugBank，and GeneCards databases were used to obtain the targets associated with hyperthyroidism.The intersecting targets of drug targets and disease targets were used as potential targets，and STRING database was used to obtain the target-protein interaction network，which was imported into Cytoscape software to obtain key targets and effective constituents.The gene ontology functional enrichment analysis and the Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were performed，and molecular docking was performed for validation.Results：A total of 50 active components were obtained，with 162 intersecting targets with hyperthyroidism.A total of 12 core targets were obtained by Cytoscape software for Sihai Shuyu pills in the treatment of hyperthyroidism，including PTPN11，IGF1R，PIK3CA，EGFR，and AKT1.The enrichment analyses showed that Sihai Shuyu pills exerted a therapeutic effect on hyperthyroidism via the the PI3K/Akt signaling pathway and the HIF-1 signaling pathway，and molecular docking showed that deoxyelephantopin，obacunone，and oxyberberine showed a relatively strong molecular binding activity to the core treatment targets，which provided an important material basis for Sihai Shuyu pills in the treatment of hyperthyroidism.Conclusion：The effective constituents of Sihai Shuyu pills exert a therapeutic effect on hyperthyroidism by regulating multiple hyperthyroidism-related targets and mediating multiple signaling pathways. |
| Key words: hyperthyroidism iodine-rich traditional Chinese medicine drugs network pharmacology molecular docking |
